The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age ...of 2 years.
The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.
Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.
Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.
The primary cause of death from breast cancer is the progressive growth of tumors and resistance to conventional therapies. It is currently believed that recurrent cancer is repopulated according to ...a recently proposed cancer stem cell hypothesis. New therapeutic strategies that specifically target cancer stem-like cells may represent a new avenue of cancer therapy. We aimed to discover novel compounds that target breast cancer stem-like cells. We used a dye-exclusion method to isolate side population (SP) cancer cells and, subsequently, subjected these SP cells to a sphere formation assay to generate SP spheres (SPS) from breast cancer cell lines. Surface markers, stemness genes, and tumorigenicity were used to test stem properties. We performed a high-throughput drug screening using these SPS. The effects of candidate compounds were assessed in vitro and in vivo. We successfully generated breast cancer SPS with stem-like properties. These SPS were enriched for CD44(high) (2.8-fold) and CD24(low) (4-fold) cells. OCT4 and ABCG2 were overexpressed in SPS. Moreover, SPS grew tumors at a density of 10(3), whereas an equivalent number of parental cells did not initiate tumor formation. A clinically approved drug, niclosamide, was identified from the LOPAC chemical library of 1,258 compounds. Niclosamide downregulated stem pathways, inhibited the formation of spheroids, and induced apoptosis in breast cancer SPS. Animal studies also confirmed this therapeutic effect. The results of this proof-of-principle study may facilitate the development of new breast cancer therapies in the near future. The extension of niclosamide clinical trials is warranted.
Using DNA methylation biomarkers in cancer detection is a potential direction in clinical testing. Some methylated genes have been proposed for cervical cancer detection; however, more reliable ...methylation markers are needed. To identify new hypermethylated genes in the discovery phase, we compared the methylome between a pool of DNA from normal cervical epithelium (n = 19) and a pool of DNA from cervical cancer tissues (n = 38) using a methylation bead array. We integrated the differentially methylated genes with public gene expression databases, which resulted in 91 candidate genes. Based on gene expression after demethylation treatment in cell lines, we confirmed 61 genes for further validation. In the validation phase, quantitative MSP and bisulfite pyrosequencing were used to examine their methylation level in an independent set of clinical samples. Fourteen genes, including ADRA1D, AJAP1, COL6A2, EDN3, EPO, HS3ST2, MAGI2, POU4F3, PTGDR, SOX8, SOX17, ST6GAL2, SYT9, and ZNF614, were significantly hypermethylated in CIN3+ lesions. The sensitivity, specificity, and accuracy of POU4F3 for detecting CIN3+ lesions were 0.88, 0.82, and 0.85, respectively. A bioinformatics function analysis revealed that AJAP1, EDN3, EPO, MAGI2, and SOX17 were potentially implicated in β‐catenin signaling, suggesting the epigenetic dysregulation of this signaling pathway during cervical cancer development. The concurrent methylation of multiple genes in cancers and in subsets of precancerous lesions suggests the presence of a driver of methylation phenotype in cervical carcinogenesis. Further validation of these new genes as biomarkers for cervical cancer screening in a larger population‐based study is warranted.
What's New?
The identification of novel genes that are hypermethylated in cancer and precancerous lesions is needed in order to achieve a better sensitivity and specificity in cervical cancer screening. Using a genome‐wide approach, here the authors identified 14 genes that were frequently hypermethylated in CIN3+ and might thus become useful biomarkers in future molecular cervical cancer screening. A bioinformatics function analysis revealed that five of these genes were potentially implicated in β‐catenin signaling, suggesting the epigenetic dysregulation of Wnt signaling during cervical cancer development. The concurrent hypermethylation of multiple genes also suggests the involvement of a CpG island methylator phenotype.
Myometrial invasion affects the prognosis of endometrial cancer. However, discrepancies exist between pre-operative magnetic resonance imaging staging and post-operative pathological staging. This ...study aims to validate the accuracy of artificial intelligence (AI) for detecting the depth of myometrial invasion using a deep learning technique on magnetic resonance images. We obtained 4896 contrast-enhanced T1-weighted images (T1w) and T2-weighted images (T2w) from 72 patients who were diagnosed with surgico-pathological stage I endometrial carcinoma. We used the images from 24 patients (33.3%) to train the AI. The images from the remaining 48 patients (66.7%) were used to evaluate the accuracy of the model. The AI then interpreted each of the cases and sorted them into stage IA or IB. Compared with the accuracy rate of radiologists’ diagnoses (77.8%), the accuracy rate of AI interpretation in contrast-enhanced T1w was higher (79.2%), whereas that in T2w was lower (70.8%). The diagnostic accuracy was not significantly different between radiologists and AI for both T1w and T2w. However, AI was more likely to provide incorrect interpretations in patients with coexisting benign leiomyomas or polypoid tumors. Currently, the ability of this AI technology to make an accurate diagnosis has limitations. However, in hospitals with limited resources, AI may be able to assist in reading magnetic resonance images. We believe that AI has the potential to assist radiologists or serve as a reasonable alternative for pre-operative evaluation of the myometrial invasion depth of stage I endometrial cancers.
To determine whether genetic predisposition to endometriosis varies depending on ethnicity and in association with expression quantitative trait loci (eQTL) in a Taiwanese population. We conducted a ...genome-wide association study (GWAS) and replicated it in 259 individuals with laparoscopy-confirmed stage III or IV endometriosis (cases) and 171 women without endometriosis (controls). Their genomic DNA was extracted from blood and evaluated by the GWAS of Taiwan Biobank Array. Novel genetic variants that predispose individuals to endometriosis were identified using GWAS and replication, including rs10739199 (P = 6.75 × 10
) and rs2025392 (P = 8.01 × 10
) at chromosome 9, rs1998998 (P = 6.5 × 10
) at chromosome 14, and rs6576560 (P = 9.7 × 10
) at chromosome 15. After imputation, strong signals were exhibited by rs10822312 (P = 1.80 × 10
) at chromosome 10, rs58991632 (P = 1.92 × 10
) and rs2273422 (P = 2.42 × 10
) at chromosome 20, and rs12566078 (P = 2.5 × 10
) at chromosome 1. We used the Genotype-Tissue Expression (GTEx) database to observe eQTL. Among these SNPs, the cis-eQTL rs13126673 of inturned planar cell polarity protein (INTU) showed significant association with INTU expression (P = 5.1 × 10
). Moreover, the eQTL analysis was performed on endometriotic tissues from women with endometriosis. The expression of INTU in 78 endometriotic tissue of women with endometriosis is associated with rs13126673 genotype (P = 0.034). To our knowledge, this is the first GWAS to link endometriosis and eQTL in a Taiwanese population.
Aldehyde dehydrogenase 1 (ALDH1) and CD44 have been established as biomarkers for predicting the survival of many types of cancer patients. This study evaluated the expression and clinical ...significance of these putative cancer-cell markers in a series of tumor samples from endometrial cancer (EC) patients using tissue microarray. We examined 245 endometrial samples, including 132 (53.87%) pre-malignancy lesions and 113 (46.12%) malignant endometrial lesions from biopsies or hysterectomies. We examined the expression of CD44 and ALDH1 in these samples using immunohistochemistry staining. Correlations in the relative expression of these markers with clinicopathological parameters were also assessed. A high level of expression of ALDH1 was found in 44.25% (50/113) of the endometrial cancer samples, which was significantly correlated with a poor overall survival rate (p = 0.035). High-level CD44 expression was found in 35.4% (40/113) of the cases and was also correlated with a poor overall survival rate (p = 0.035). A simultaneous high expression of both markers was correlated with an extremely poor overall survival (p = 0.013). Our results show that tumors with higher expressions of both ALDH1 and CD44 were related to a poorer overall survival rate among EC patients. The combination of ALDH1 and CD44 could be a promising marker for developing additional targeted therapy for severe endometrial cancers.
Huge or enlarged solid ovarian tumor, elevated serum CA‑125 levels, massive ascites, and even pleural effusions are common features of ovarian cancer which have the worst outcome of gynecological ...malignancy. Here, we report a 53‑year‑old woman with fibrothecoma‑associated Meigs syndrome mimicking ovarian malignancy, whose symptoms resolved gradually, and subsequently, serum CA‑125 level declined to normal range after surgical intervention. The pathological diagnosis revealed fibrothecoma of the ovary compatible with Meigs syndrome containing the triad of benign ovarian tumor, ascites, and pleural effusion. Therefore, Meigs syndrome should be considered one of the clinical differential diagnoses for a large ovarian tumor with ascites, pleural effusion, and elevated CA‑125.
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